Osteoarthritis is a prevalent and costly disease, second only to cardiovascular disease in producing severe chronic disability. Because it is extremely difficult to study osteoarthritis in its early stages in human beings, study of an appropriate animal model of naturally occurring disease is necessary to understand its pathogenesis. This laboratory has recently identified a high level of naturally occurring osteoarthritis, with morphologic features very similar to those seen in human beings, in the knee joints of captive female cynomolgus monkeys (Macaca fascicularis). The objectives of this project are to further characterize osteoarthritis in these animals; to develop and implement a quantitative grading scheme to assess lesion severity; and, using this scheme, to determine the effects of estrogen deficiency and androgenic hormone treatment on the disease.